A modified matrix perfusion-microcarrier bead cell culture system. II. Production of human (beta) interferon in a...

Addition of microcarrier beads to a matrix perfusion cell culture system allowed growth of anchorage dependent human foreskin fibroblasts which would not grow in the culture units alone. The utility of the system for collection of cellular products was demonstrated by the induction and harvesting of human (beta) interferon. Interferon production was highest in perfusion cultures when medium was circulated throughout the induction and when inducer containing 100 mug/mL polyriboinosinic: polyribocytidylic acid was placed directly in contact with cells in the extracapillary space. These conditions provided 4-to-10-fold greater interferon yields per cell, and approximately 12-fold increases per vessel, than monolayer cultures. Perfusion grown cells produced interferon at a maximal level for 20 h postinduction compared to approximately 2 h for monolayer grown cells, thus giving a higher total yield of interferon. Other procedures increasing the efficiency of the system included priming with 50 U/mL interferon standard, reinduction of cells, use of antibiotic free medium, reduced serum concentrations, and in vitro aging of the cells.